Ubiquinol is the 2e−-reduced form of ubiquinone which is a benzoquinone derivative distributed broadly in the living world. Ubiquinol and ubiquinone, both of which are localized in mitochondria, lysosomes, Golgi bodies, microsomes, peroxisomes, cell membranes, etc., are substances indispensable for the maintenance of biological functions as constituents of the electron transport system, and are known to be involved in activation of ATP production, antioxidant activity in the living body, and membrane stabilization. Paying attention to its vitamin-like function, ubiquinone is also called as vitamin Q, which is a factor capable of rejuvenating the body as a nutrient for reinstating depressed cell activity to healthy state.
In the living body, ubiquinol and ubiquinone are in a certain equilibrium state, and it is known that the ubiquinol/ubiquinone absorbed into the body are mutually oxidized/reduced. It is reported that usually, in the living body, ubiquinol accounts for 60 to 90% of the total weight of ubiquinol and ubiquinone.
Since ubiquinone is not only supplied from diets but also biosynthesized in the body, it might be considered that the necessary amount of ubiquinol and ubiquinone is available in the normal state but it is known that actually the ubiquinol/ubiquinone content in the body is markedly decreased due to aging and various stresses to which the living body is subjected.
For example, it is reported that whereas the ubiquinone content in the human heart in the 19 to 21 years of age is 110.0 μg/g, the content is drastically reduced to less than one-half, namely 47.2 μg/g, in the 77 to 81 years of age [Kalen, A. et al., Lipids, 24, 579-584 (1989)]. Moreover, the ubiquinone content in plasma is decreased in uremic patients, patients under chronic hemodialysis treatment, and patients with various allergic diseases as compared with healthy persons (Triolo, L., Nephron, 66, 153-156 (1994); Folkers, K., BioFactors, 1, 303-306 (1988)]. In patients with hyperlipemia, the ubiquinone content in the LDL cholesterol fraction is decreased [Kontush, A., et al., Atherosclerosis, 129, 119-126 (1997)]. Furthermore, it has been pointed out that administration of cholesterol synthesis inhibitors which are in common use today as therapeutic drugs for hypercholesterolemia inhibits the biosynthesis of ubiquinone as well, causing decrease in ubiquinone concentration in tissues [E. L. Appelkvist et al., Clinical Investigator, 71, S97-S102 (1993)]. In addition, decreases in the tissue concentration are suspected under conditions where peroxides are easily produced in the living body, such as strenuous exercises or overfatigue.
Decreases in the ubiquinol and ubiquinone content in the body characteristically lead to decreases in ATP productivity and cardiac function, decreased resistance to oxidation stress, and instability of the biomembranes, thus being deleterious to health. To make up for a shortage of ubiquinol and ubiquinone is benefit for promoting energy production in mitochondria, enhancing the antioxidant capacity of the living body, and maintenance of homeostasis.
Ubiquinone is expected to exhibit efficacy in the amelioration and/or prevention of diseases of the heart, hypertension, obesity, diabetes, cancer, Parkinson's disease, periodontal diseases, neuropathy, allergies, reproductive potential, exercise tolerance, immune functions, fatigue, and the like.
For example, elevation of the cardiac function due to administration of ubiquinone has been reported [Kishi, T. et al., Clin. Investg., 71, S71-S75 (1993)]; ameliorating efficacy in cardiac diseases such as congestive heart failure, angina pectoris, myocardial infarction, etc. by ubiquinone [Singh, R. B. et al., Inter. J. Cardiology, 68, 23-29 (1999), Singh, R. B. et al., Cardiovasc. Drugs Ther., 12, 347-353 (1998)]; preventive and ameliorative efficacy in atherosclerosis, hypertension, diabetes, cancer, periodontal diseases, and allergies [Singh, RB. et al., Atherosclerosis, 148, 275-282 2000, Digiesi, V., et al., Curr. Therap. Res., 51, 668-672 (1992), Kishi, T., et al., Journal of Dental Health, 43, 667-672 (1993), Shimura Y., et al., Rinsho-to-Kenkyu, 58, 1349-1352 (1981)]; reproductive potential-improving effect, inhibition of oxidation of LDL cholesterol, dialysis frequency-reducing effect in renal dialysis patients, nonspecific immunity-potentiating effect, and the like are known [Stocker et al., Mol. Aspects Med., 18, S85-S103 (1997), Lippa, S., Mol. Aspects Med., 15, S213-S219 (1994)]. Furthermore, ubiquinone is already in use clinically as a therapeutic drug for the palpitation, short breadth, and anasarca arising from congestive heart failure or mild heart diseases.
In order to make up for the deficiencies in ubiquinol and ubiquinone in the living body which occur in the daily activity of living, it is necessary to supply the ubiquinone appropriately. In cases of the oxidation stress disturbance pointed out to occur in excessive exercises, not only in persons of the middle age to elderly persons but also in young individuals, the ubiquinol content is decreased and it is, therefore, important to enhance the antioxidant capacity of the body by ubiquinol feeding. To enhance the ubiquinol content in the living body, it has for some time been attempted to supply an exogenous ubiquinone.
As means for feeding the ubiquinone which tend to become decreased and fall short of the requirements in daily lives despite their being indispensable for the maintenance of biological functions as mentioned above, it has already been practiced to supply this substance as a drug or as a food supplement in the form of tablets or capsules but for healthy or semi-healthy persons in whom deficiencies are slight and unqualified for medical care, and the like persons, it is more convenient to take this substance in the same ways as the ordinary food than taking it in the form of tablets or capsules.
The ubiquinol/ubiquinone content in food is usually measured as the ubiquinone content which is easy to determine. According to the available data, whereas ubiquinone is known to occur broadly in many ordinary foodstuffs of the animal or vegetable origin, such as meats, fish meats, cereals, vegetables, fruits, and eggs, the content is generally low except in beef in which it is as high as 30 μg/g, and the like. For example, the said content is as low as about 1.5 μg/g in hen's eggs, about 1.1 μg/g in wheat breads, and about 0.52 μg/g in potatoes, so that the daily ingestion from the usual diets is about 3 to 5 mg. Furthermore, the absorption rate of ubiquinone after oral ingestion is low, so that with the ordinary foods taken in the usual manner, it is not easy to achieve ubiquinol/ubiquinone supply.
Since ubiquinone and ubiquinol are considered to be in equilibrium state in the living body, if the ubiquinone-enriched food is utilized in such a situation, it seems possible to supply ubiquinol and ubiquinone in which one is liable to be deficient but only a few kinds of ubiquinol- or ubiquinone-enriched foods have been available to this day. As regards a ubiquinone-containing food, we know only of Japanese Kokai Publication Hei-10-45614 entitled “Blood coagulation-inhibitory food for diet therapy and drug”, and the like, but there is not a case in which food is ever supplemented with ubiquinol. Japanese Kokai Publication Hei-10-45614, referred to above, discloses a blood coagulation-inhibitory food for diet therapy which comprises corn germ oil which is rich in ubiquinone but, in this art, the ubiquinone inherently contained in corn germ oil is utilized and contemplation about enrichment of food with ubiquinone is not described.
Meanwhile, ubiquinol has not attracted much attention because it is in some kind of equilibrium with ubiquinone in the living body but recent years have witnessed several reports arguing that ubiquinol is more effective than ubiquinone in several applications. For example, it has been reported that ubiquinol is more efficient than ubiquinone in oral absorption (Japanese Kokai Publication Hei-10-109933) and that ubiquinols are effective in the amelioration and prevention of hypercholesterolemia, hyperlipemia, and atherosclerosis (Japanese Kokai Publication Hei-10-330251). However, the ingestion of a ubiquinol-enriched food has not been known yet.
While it is important to supply ubiquinol and ubiquinone which are indispensable to the living body but are liable to be decreased and fall short of the requirements, the following points are especially worth attention as the reasons why ubiquinol- or ubiquinone-enriched foods are not in popular use or hardly popularized.
(1) Ubiquinol is highly absorbable orally and more effective than ubiquinone but since ubiquinol is an unstable compound which is readily converted to ubiquinone by air oxidation, it is not easy to enrich foods with ubiquinol in a stabilized manner.
(2) Ubiquinone is low in oral absorbability.
(3) The source of the antioxidant activity is ubiquinol. Thus, because ubiquinol is oxidized to ubiquinone, a deficiency in ubiquinol occurs, rather than a deficiency in ubiquinone, in oxidation stress disturbance.
(4) When ubiquinone or ubiquinol is merely added to food, it cannot be uniformly dissolved or dispersed and even if uniformly dissolved or dispersed once, it will separate out during storage or be localized within the food to adversely affect the flavor, texture and appearance of the food, thus failing to provide a fully satisfiable food product.
Under such circumstances, if the above-mentioned drawbacks (1) and (4) are overcome, it will be possible to develop and provide meritorious foods with which ubiquinol may be supplied with ease and good efficiency.